Nigeria, the top performers so far in the ongoing Africa Cup of Nations in Cameroon, were paired with arch-rivals Ghana in the African World Cup play-offs draw in Douala on Saturday.
Ghana will have home advantage first and both legs will be played between March 21 and 29 with the aggregate winners securing a place at the 2022 World Cup in Qatar.
Egypt face Senegal, Cameroon meet Algeria, the Democratic Republic of Congo play Morocco and Mali tackle Tunisia in the other ties.
Only Mali among the 10 contenders have never qualified for the world football showpiece while Cameroon hold the record for appearances by an African team with seven between 1982 and 2014.
Nigeria brushed off a troubled build-up to the Cup of Nations, including the sacking of German coach Gernot Rohr, to be the only team among the 24 in Cameroon to win all three group matches.
While the Super Eagles look forward to a last-16 clash with Tunisia on Sunday, Ghana were shock first-round casualties, finishing bottom of a group after a stunning 3-2 loss to minnows the Comoros.
Algeria, the defending champions and shock early departees from the tournament, will face Cameroon, another in-form team with captain Vincent Aboubakar scoring five times in three group games.
Mali will fancy their chances of a historic first appearance at the finals after defeating Tunisia in Cameroon last week through an Ibrahima Kone penalty.
Egypt v Senegal
Cameroon v Algeria
Ghana v Nigeria
Democratic Republic of Congo v Morocco
Mali v Tunisia